The broad objective of this proposal lies in the utilization of cultured cells for the study of various aspects of human genetics and immunology. Four general areas of study are being used although various experiments may coordinate efforts under several of these headings. Cytogenetics: We are continuing to enlarge our collection of chromosomal variants and use the standard techniques, as well as the newer techniques for chromosome identification. We are studying the range of chromosomal aberrations associated with congenital anomalies. We are continuing our study on cultured oocytes to identify aging effects. Biochemical Genetics: We are continuing to develop more assay techniques for the ascertainment of inborn errors of metabolism and to apply these techniques to cultured cells. We are particularly interested in the study of cultured amniotic fluid cells for the purpose of more accurate prenatal diagnosis. Somatic Cell Genetics: We are continuing our study of gene linkage using both the established methods and our more recently devised method of mRNA hybridization with the DNA of the karyotype. We are also attempting to purify individual groups of chromosomes in order to attempt genetic transformation of cultured cells. Lymphocyte Studies: We are studying the lymphocyte response in short-term cultures to phyto-hemagglutinin and specific antigens and are establishing a library of long-term lines from patients with and heterozygous for heritable disorders including those of the immune response.